Handbook of drug interactions: a clinical and forensic guide

662 Pages·2004·5.963 MB·English

by  Ashraf Mozayani, Lionel P. Raymon

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Handbook of Drug Interactions
F O R E N S I C
S C I E N C E A N D M E D I C I N E
Steven B. Karch, MD, SERIES EDITOR
HANDBOOK OF DRUG INTERACTIONS: A CLINICAL AND FORENSIC GUIDE,
edited by Ashraf Mozayani and Lionel P. Raymon, 2004
DIETARY SUPPLEMENTS: TOXICOLOGY AND CLINICAL PHARMACOLOGY,
edited by Melanie Johns Cupp and Timothy S. Tracy, 2003
BUPRENOPHINE THERAPY OF OPIATE ADDICTION,
edited by Pascal Kintz and Pierre Marquet, 2002
BENZODIAZEPINES AND GHB: DETECTION AND PHARMACOLOGY,
edited by Salvatore J. Salamone, 2002
ON-SITE DRUG TESTING,
edited by Amanda J. Jenkins and Bruce A. Goldberger, 2001
BRAIN IMAGING IN SUBSTANCE ABUSE: RESEARCH, CLINICAL, AND FORENSIC APPLICATIONS,
edited by Marc J. Kaufman, 2001
TOXICOLOGY AND CLINICAL PHARMACOLOGY OF HERBAL PRODUCTS,
edited by Melanie Johns Cupp, 2000
CRIMINAL POISONING: INVESTIGATIONAL GUIDE FOR LAW ENFORCEMENT,
TOXICOLOGISTS, FORENSIC SCIENTISTS, AND ATTORNEYS,
by John H. Trestrail, III, 2000
A PHYSICIAN’S GUIDE TO CLINICAL FORENSIC MEDICINE,
edited by Margaret M. Stark, 2000
RRH iii
H
ANDBOOK
D
OF RUG
I
NTERACTIONS
A C F G
LINICAL AND ORENSIC UIDE
Edited by
Ashraf Mozayani, PharmD, PhD
Harris County Medical Examiner Office, Houston, TX
and
Lionel P. Raymon, PharmD, PhD
University of Miami School of Medicine, Miami, FL
© 2004 Humana Press Inc.
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All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or
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The content, opinions, and points of view expressed in this book are the sole work of the authors and editors, who have
warranted due diligence in the creation and issuance of their work. These views are not necessarily the views of the
organizations with whom the authors are employed (or otherwise associated). The publisher, editors, and authors are
not responsible for errors or omissions or for any consequences arising from the information or opinions presented in
this book and make no warranty, express or implied, with respect to its contents.
Production Editor: Mark J. Breaugh.
Cover illustration: Two complementary views of drug interactions. The mathematical modeling of the drug is shown
as a classic first order kinetic elimination curve and alteration in pharmacokineticsis amongst the best understood
potential for undesired effects from combinations of two or more pharmaceuticals. But harder to grasp are the dynamic
effects of drugs. The results of binding to target proteins, such as ion channels, can change the overall activity of cells,
such as neurons, which in turn impinge on other target tissues. These pharmacodynamic interactions are complex and
culminate in the symptomology observed in the patient. Any combination of chemicals in the body, endogenous or
not,is a fluidgame of competitions, synergies, or antagonisms at the metabolic and functional level. The results may
go unseen, may be beneficial, may be harmfulor,in some cases,lethal to the subject.
Cover design by Patricia F. Cleary.
Due diligence has been taken by the publishers, editors, and authors of this book to ensure the accuracy of the information
published and to describe generally accepted practices. The contributors herein have carefully checked to ensure that
the drug selections and dosages set forth in this text are accurate in accord with the standards accepted at the time of
publication. Notwithstanding, as new research, changes in government regulations, and knowledge from clinical expe-
rience relating to drug therapy and drug reactions constantly occurs, the reader is advised to check the product information
provided by the manufacturer of each drug for any change in dosages or for additional warnings and contraindications.
This is of utmost importance when the recommended drug herein is a new or infrequently used drug. It is the respon-
sibility of the health care provider to ascertain the Food and Drug Administration status of each drug or device used in
their clinical practice. The publisher, editors, and authors are not responsible for errors or omissions or for any conse-
quences from the application of the information presented in this book and make no warranty, express or implied, with
respect to the contents in this publication.
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Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1
E-ISBN: 1-59259-654-1
Library of Congress Cataloging-in-Publication Data
Handbook of drug interactions : a clinical and forensic guide / [edited
by] Ashraf Mozayani, Lionel P. Raymon.-- 1st ed.
p. ; cm. -- (Forensic science and medicine)
Includes bibliographical references and index.
ISBN 1-58829-211-8 (alk. paper)
1. Drug interactions--Handbooks, manuals, etc. 2. Forensic
pharmacology--Handbooks, manuals, etc.
[DNLM: 1. Drug Interactions--Handbooks. 2. Forensic
Medicine--methods--Handbooks. 3. Medication Errors--Handbooks. 4.
Pharmacokinetics--Handbooks. QV 39 H23635 2003] I. Mozayani, Ashraf.
II. Raymon, Lionel P. III. Series.
RM302.H344 2003
615'.7045--dc21
2003008434
RRH v
Preface
Drug interactions and adverse drug effects have received much attention since studies
published in daily newspapers have shown that they result in upwards of 100,000
Americans each year being hospitalized or remaining hospitalized longer than necessary,
as well as leading to the death of a number of patients. Use of multiple drugs (8–12 on
average in hospitalized patients) is common in a number of therapeutic regimens. In
addition to multiple drug therapy, a patient may have access to several prescribers, and
may have predisposing illnesses or age as risk factors for interactions. Drug interactions
may occur between prescription drugs, but also between food and drug, and chemical
and drug. Whereas some may be adverse, interactions may also be sought to decrease
side effects or to improve therapeutic efficacy.
Combining drugs may cause pharmacokinetic and/or pharmacodynamic interactions.
Pharmacokinetic mechanisms of interaction include alterations of absorption, distribution,
biotransformation, or elimination. Absorption can be altered when drugs that alter pH or
motility are co-administered, as seen with certain antiulcer or antidiarrheal medications,
or when drugs are chelators or adsorbents (tetracyclines and divalent cations,
cholestyramine, and anionic drugs). Distribution variations can result from competition
for protein binding (sulfa drugs and bilirubin binding to albumin) or displacement from
tissue-binding sites (digitalis and calcium channel blockers or quinidine). Induction of
gene expression (slow), activation or inhibition (much quicker) of liver and extrahepatic
enzymes such as P450, and conjugating enzymes have long found a place of choice in
the literature describing the potential for adverse drug interactions resulting from altered
metabolism. For example, induction is well described with the major anticonvulsant
medications phenytoin, carbamazepine, and barbiturates, whereas inhibition can occur
with antimicrobials from the quinolone, the macrolide, and the azole families. Finally,
excretion can also be modified by drugs that change urinary pH, as carbonic anhydrase
inhibitors do, or change secretion and reabsorption pathways, as probenecid does.
Pharmacokinetic interactions in general result in an altered concentration of active drug
or metabolite in the body, modifying the expected therapeutic response.
A second form of interaction has received little attention because of its modeling
complexity and perhaps the poor understanding of basic physiological, biochemical, and
anatomical substrates for drug action. Pharmacodynamic interactions involve additive
(1+1=2), potentiating (0+1=2), synergistic (1+1=3), or antagonistic (1+1=0)
v
vi Preface
effects at the level of receptors. Receptors are mainly proteins, such as enzymes
(acetylcholinesterase, angiotensin-converting enzyme, for example), transport proteins
(digitalis and Na+/K+ ATPase), structural proteins (colchicine and tubulin), or ion channels
(Class I antiarrhythmics and voltage-dependent sodium channels). Large families of
receptors to drugs involve signal transduction pathways and changes in intracellular second
messenger concentrations (autonomic nervous system drugs and α, β, muscarinic receptors,
for example). Finally, even less understood are interactions at the level of nucleic acids
such as DNA and RNA, which can change the levels of expression of key proteins in target
tissues (tolerance, tachyphylaxis of numerous central nervous system drugs).
Handbook of Drug Interactions: A Clinical and Forensic Guide addresses both
types of drug interactions, emphasizing explanations when possible, and careful review
of the general pharmacology. The result, we hope, will prove useful to health and forensic
professionals as well as medical, pharmacy, nursing and graduate students alike.
Ashraf Mozayani
Lionel P. Raymon
RRH vii
Contents
Preface ................................................................................................................v
Contributors.......................................................................................................ix
P I C N S D
ART ENTRAL ERVOUS YSTEM RUGS
Chapter 1: Drug Interactions with Benzodiazepines:
Epidemiologic Correlates with Other CNS Depressants
and In Vitro Correlates with Inhibitors and Inducers
of Cytochrome P450 3A4............................................................ 3
David E. Moody
Chapter 2: Antiepileptic Drugs ......................................................................89
Nathan L. Kanous II and Barry E. Gidal
Chapter 3: Opioids and Opiates ...................................................................123
Seyed-Adel Moallem, Kia Balali-Mood, and Mahdi Balali-Mood
Chapter 4: Monoamine Oxidase Inhibitors and Tricyclic Antidepressants ......149
Terry J. Danielson
Chapter 5: Selective Serotonin Reuptake Inhibitors ....................................175
Mojdeh Mozayani and Ashraf Mozayani
Chapter 6: Antipsychotic Drugs and Interactions:
Implications for Criminal and Civil Litigation ...................... 187
Michael Welner
P II C D
ART ARDIOVASCULAR RUGS
Chapter 7: Cardiovascular Drugs .................................................................219
Johann Auer
P III A
ART NTIBIOTICS
Chapter 8: Antimicrobial Drugs...................................................................295
Amanda J. Jenkins and Jimmie L. Valentine
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viii Contents
Chapter 9: Drug Interactions with Medications Used for HIV/AIDS..........319
Michael Frank
P IV N A D
ART ONSTEROIDAL NTIINFLAMMATORY RUGS
Chapter 10: Nonsteroidal Antiinflammatory Drugs:
Cyclooxygenase Inhibitors, Disease-Modifying
Antirheumatic Agents, and Drugs Used in Gout .................... 337
Imad K. Abukhalaf, Daniel A. von Deutsch, Mohamed A. Bayorh,
and Robin R. Socci
P V E S P
ART NVIRONMENTALAND OCIAL HARMACOLOGY
Chapter 11: Food and Drug Interactions........................................................379
Shahla M. Wunderlich
Chapter 12: Alcohol and Drug Interactions ...................................................395
A. Wayne Jones
Chapter 13: Nicotine and Tobacco .................................................................463
Edward J. Cone, Reginald V. Fant, and Jack E. Henningfield
Chapter 14: Anabolic Doping Agents ............................................................493
Daniel A. von Deutsch, Imad K. Abukhalaf, and Robin R. Socci
P VI L A
ART EGAL SPECTS
Chapter 15: Drug Interaction Litigation.........................................................599
Stephen A. Brunette
Chapter 16: Psychotropic Medications and Crime:
The Seasoning of the Prozac Defense.....................................631
Michael Welner
Index...............................................................................................................647
RRH ix
Contributors*
IMAD K. ABUKHALAF, PhD • Department of Pharmacology and Toxicology, NASA
Space Medicine and Life Sciences Research Center; Clinical Research Center,
Morehouse School of Medicine, Atlanta, GA; Department of Biotechnology and
Genetic Engineering, Philadelphia University, Amman, Jordan.
JOHANN AUER, MD • Department of Cardiology and Intensive Care, General Hospital
Wels, Wels, Austria
KIA BALALI-MOOD, PhD • Laboratory of Membrane Biophysics, Division of Pre
Clinical Veterinary Sciences, The Vet School, College of Medicine & Veterinary
Medicine, University of Edinburgh, Edinburgh, UK
MAHDI BALALI-MOOD, MD, PhD • Medical Toxicology Centre, Imam Reza Hospital,
Mashad, Iran
MOHAMED A. BAYORH, PhD • Department of Pharmacology and Toxicology, NASA
Space Medicine and Life Sciences Research Center; Cardiovascular-Alteration Team,
National Space Biomedical Research Institute, Morehouse School of Medicine,
Atlanta, GA
STEPHEN A. BRUNETTE, PC • Stephen A. Brunette, P. C., Colorado Springs, CO
EDWARD J. CONE, PhD • Pinney Associates, Bethesda, MD; Johns Hopkins University,
Baltimore, MD
TERRY J. DANIELSON, PhD • Harris County Medical Examiner Office, Houston, TX
REGINALD V. FANT, PhD • Pinney Associates, Bethesda, MD
MICHAEL FRANK, MD • Division of Infectious Diseases, Medical College of Wisconsin,
Milwaukee, WI
BARRY E. GIDAL, PharmD • Department of Neurology, School of Pharmacy, University
of Wisconsin at Madison, Madison, WI
JACK E. HENNINGFIELD, PhD • Pinney Associates, Bethesda, MD; Department of
Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine,
Baltimore, MD
AMANDA J. JENKINS, PhD • The Office of the Cuyahoga County Coroner, Cleveland, OH
A. WAYNE JONES, PhD, DSc • Department of Forensic Toxicology, University Hospital,
Linköping, Sweden
ix